Monitoring drug–protein interaction

Yang, Xiao; Hu, Zeping; Chan, Sui Yung; Zhou, Shu Feng

doi:10.1016/j.cca.2005.08.021

Cited by 37 publications

(23 citation statements)

References 241 publications

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“…This could be of interest because IDRs usually have a delayed onset of occurrence and seem to take place essentially in patients taking a drug in relatively high doses for a longer period of time. In this perspective, this strategy may also be seen as an in vivo dosimetry methodology to assess levels of covalent binding to proteins (Yang et al, 2006). Consequently, this technology could constitute a potential biomonitoring tool that could improve the risk assessment of ADRs and IDRs of novel drugs and/or drug candidates.…”

Section: Adductmentioning

confidence: 99%

Liquid Chromatography/Tandem Mass Spectrometry Detection of Covalent Binding of Acetaminophen to Human Serum Albumin

Damsten¹,

Commandeur²,

Fidder³

et al. 2007

Drug Metab Dispos

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ABSTRACT:Covalent binding of reactive electrophilic intermediates to proteins is considered to play an important role in the processes leading to adverse drug reactions and idiosyncratic drug reactions. Consequently, both for the discovery and the development of new drugs, there is a great interest in sensitive methodologies that enable the detection of covalent binding of drugs and drug candidates in vivo. In this work, we present a strategy for the generation and analysis of drug adducts to human serum albumin. Our methodology is based on the isolation of albumin from blood, its digestion to peptides by pronase E, and the sensitive detection of adducts to the characteristic cysteine-proline-phenylalanine (CPF) tripeptide by liquid chromatography/tandem mass spectrometry. We chose acetaminophen (APAP) as a model compound because this drug is known to induce covalent binding to proteins when bioactivated by cytochromes P450 to its reactive N-acetyl-p-benzoquinoneimine metabolite. First, by microsomal incubations of APAP in presence of CPF and/or intact albumin, in vitro reference adducts were generated to determine the mass spectrometric characteristics of the expected CPF adducts and to confirm their formation on pronase E digestion of the alkylated protein. When applying this methodology to albumin isolated from blood of patients exposed to APAP, we were indeed able to detect the corresponding CPF adducts. Therefore, this strategy could be seen as a potential biomonitoring tool to detect in vivo reactive intermediates of drugs and drug candidates, e.g., in the preclinical and clinical development phase.

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Section: Adductmentioning

confidence: 99%

Liquid Chromatography/Tandem Mass Spectrometry Detection of Covalent Binding of Acetaminophen to Human Serum Albumin

Damsten¹,

Commandeur²,

Fidder³

et al. 2007

Drug Metab Dispos

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“…The distribution, free concentration and the metabolism of various drugs may be strongly affected by drug-protein interaction in the bloodstream [9,10]. Moreover, the determination and monitoring of drug-protein adducts have important clinical, pharmacological and toxicological implications [11]. UV spectrometry [12][13][14][15] and electrochemical methods [6,[16][17][18][19] have been generally used in the studies on the interaction of drug-protein.…”

Section: Introductionmentioning

confidence: 99%

Voltammetric and spectroscopic studies on the interaction of tilmicosin with bovine serum albumin at different pHs

Bíçer

Özdemír

2011

Journal of Electroanalytical Chemistry

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“…One possible explanation for the disappearance of the peak is that it results from the conformational change of the protein induced by the drug. It has been suggested that the target protein can be adducted by multiple reactive species [42].…”

Section: Oxaliplatin-hb Interactionmentioning

confidence: 99%

Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

Lemma

Mandal

et al. 2008

J of Separation Science

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Original PaperInvestigation of interaction between human hemoglobin A 0 and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection CIEF with whole column imaging detection (WCID) was used to investigate the interaction of platinum-based anticancer drugs, cis-platinum(II) diamine dichloride (cisplatin) and [SP-4-2-{1R-trans)]-(1,2-cyclohexanediamine-N,N9)[ethanedioata(2 -)-O,O9]platinum (oxaliplatin), with human hemoglobin A 0 (Hb). This technique facilitates the investigation and characterization of the formation of adducts between drugs and proteins. Cisplatin and oxaliplatin were mixed with the target protein at different concentrations (0:1, 1:1, 1:10, 1:50, and 1:100), and the reaction mixtures were incubated for 0, 0.5, 1, 12, 24, 48, and 72 h at 378C in a water-bath. The focused Hb -drug adduct profiles were imaged by WCID. At higher drug to protein molar ratios (for both oxaliplatin and cisplatin), the results exhibit significant changes in the peak shapes and heights, which may indicate the destabilization of the protein. However, the conformational change was less evident at lower molar ratios. In addition, a major pI shift was observed for the oxaliplatin reaction mixtures (for 1:10, 1:50, and 1:100 ratios). In comparison with previously reported findings obtained by other analytical methods, conclusions were drawn about the validity of CIEF as a simple and convenient method for the investigation of protein -drug interactions. These results may provide useful information for further understanding the activity and toxicity of these chemotherapeutic drugs and improving their clinical performance.

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Monitoring drug–protein interaction

Cited by 37 publications

References 241 publications

Liquid Chromatography/Tandem Mass Spectrometry Detection of Covalent Binding of Acetaminophen to Human Serum Albumin

Liquid Chromatography/Tandem Mass Spectrometry Detection of Covalent Binding of Acetaminophen to Human Serum Albumin

Voltammetric and spectroscopic studies on the interaction of tilmicosin with bovine serum albumin at different pHs

Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

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Monitoring drug–protein interaction

Cited by 37 publications

References 241 publications

Liquid Chromatography/Tandem Mass Spectrometry Detection of Covalent Binding of Acetaminophen to Human Serum Albumin

Liquid Chromatography/Tandem Mass Spectrometry Detection of Covalent Binding of Acetaminophen to Human Serum Albumin

Voltammetric and spectroscopic studies on the interaction of tilmicosin with bovine serum albumin at different pHs

Investigation of interaction between human hemoglobin A0 and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

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Investigation of interaction between human hemoglobin A₀ and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection